Effect of shiga toxin-1 (Stx1) and lipopolysaccharide (LPS) on inflammatory response and apoptosis of rat astrocytes

V. LANDONI ,; C. CALATAYUD; M. CAMPOS-NEBEL; P. SCHIERLOH; PALERMO, M. S.; SASIAIN MC; M. ISTURIZ.

Rio de Janeiro, Brasil

Congreso; 13th International Congress of Immunology; 2007

International Union of Immunological Societies

Hemolytic uremic syndrome (HUS) is generally caused by E. coli producing Stxs. The pathophysiology of HUS, characterized by microangiopathic hemolytic anemia and acute renal failure, also involve the action of bacterial LPS. In addition, different neurologic symptoms could be observed in HUS patients. Although the mechanisms of neurological symptoms are not known, damage of brain endothelium, a component of the blood-brain barrier (BBB), is clear. These cells are relatively resistant to Stx but inflammatory cytokines can enhance their susceptibility. Astrocytes (ASTs) are in close contact with brain endothelium modulating the permeability of BBB by cytokines and play a role in the inflammatory response. Then, the aim of this work was to evaluate if Stx1 alone, or with LPS, is capable of inducing an inflammatory response on ASTs. ASTs activation induced by Stx1+LPS showed an increase of glial fibrillary acidic protein (GFAP) expression after 72 hs (p<0.05), and a maximal TNF-¦Á secretion after 24 hs (p<0.05). Chemotactic ability of supernatants from ASTs treated-cells was evaluated. In this sense the migration of rat neutrophils (PMN) was increased by supernatants from LPS (p<0.05), Stx1(p<0.001) and LPS+Stx-1 (p<0.001) treated ASTs. Finally, ASTs apoptosis was evaluated after 24, 48 and 72 hs of treatment. A significant induction of apoptosis was observed on LPS+Stx1-treated ASTs (p<0.05). The damage of ASTs treated with Stx1/LPS/PMN was also evaluated. Our results suggest that the response of ASTs to Stx1+LPS may contribute to inflammation and PMN migration leading to endothelial injury and disturbance of the BBB function.